Attitudes among dental students concerning dental public health as a professional career. The report has presented information about attitudes concerning Career in Dental Public Health of 722 dental students representing 19 American schools of dentistry.  "Attitude" was operationally defined by the "attractiveness" of the concept as measured in 1969 with the semantic differential technic (exciting-dull, rewarding-frustrating, successful-unsuccessful).-6  The "attractiveness" of Career in Dental Public Health was compared with that of two other concepts: Career in Private Practice and Career in Dental Education.  Specifications were made according to year of study, individual school, type of school (public or private control), geographical region of university town, and dental school relation to graduate schools of public health.  Observed differences in student attitudes at the different schools were analyzed in relation to the emphasis each school placed in 1968-69 on instruction in (dental) public health, and to the amount of experieniced instruction in (dental) public health by each individual class.


Dental students paired for DAU training. In summary, policy has been established at the University of Oklahoma College of Dentistry which pairs dental students for their clinical experiences during the first two years of their dental education--alternating the roles of dentist and assistant. A modified program for third-year dental students has been designed which includes assignment of trained dental assistants and some limited solo operations as well as a continuation of the pairing. It is anticipated that this approach will also be employed during the fourth year with more emphasis being placed upon utilization of trained assistants. The formal DAU course is given first semester of freshman year; and the principles are reinforced in each subsequent year. The advantages of this program seem to be (1) early integration of DAU principles into the curriculum, (2) increased efficiency while operating in pairs, (3) experience for training assistants for further private practice, (4) reduced appointment time for patients and (5) better use of clinical space. The application of the pairing concept will be continuously reevaluated to determine if such benefits are forthcoming.


Educational program  n dental public health at schools of public health as of fall 1973. A letter of inquiry from a fictious dentist, requesting applications and information regarding training in dental public health, was sent to each of the 19 accredited Schools of Public Health. The purpose of the survey was to determine the manner in which the schools respond to a letter of inquiry from a dentist and to determine, from the material included in the response, what type of program in dental public health, if any, each school had. All 19 schools responded, but the type and quality of the responses varied greatly. Some schools answered the questions fully and others ignored them. From the bulletins of the schools and other material contained in the responses, seven schools were determined to have what could be termed viable programs in dental public health. Two of the seven programs are administratively independent with full-time faculty as directors of their programs; three of the programs receive their major input in dental public health from an affiliated dental school; one program's input of dental public health is provided by the school of public health; and one program has an affiliation with a dental school, but the major portion of the input for dental public health during the year of preparation for the degree of MPH is provided in the school of public health. There are seven schools of public health with eight full-time faculty who are public health dentists, although only three of the faculty spend a substantial portion of their time in activities related to dental public health. Five schoolshave no public health dentist on the faculty and they have a total of 33 part-time faculty at the rank of assistant professor or higher and a total of 36 part-time faculty with a rank lower than instructor. Twelve of the schools of public health still require only a minimum of an academic year for a dentist to receive the degree of MPH and only one school requires more than a calendar year. Only five schools require field-experience in order for a dentist to receive his degree of MPH. Most schools, it appears, do not provide a program for dentists which meets the standards established by the American Public Health Association or the American Board of Dental Public Health. It is time to question the blanket acceptance by the Council on Dental Education of the American Public Health Association's accreditation of Schools of Public Health for meeting the academic requirements in the specialty of dental public health.


Fever of unknown origin and the value of gallium-67 and technetium-99M for defining abnormality of the spleen: a case report. A three-year-old white female with acute promyelocytic leukemia developed persistent fever after successful induction-remission therapy; many large monilial abscesses were later found in the grossly enlarged spleen. Although the technetium-99M sulfur colloid scan prior to splenectomy suggested only a slight abnormality of the spleen, the gallium-67 citrate scintigraph showed a marked increase in gallium accumulation. The disparate results of the scanning techniques utilized in this patient suggest that it may be necessary to use more than one type of radiopharmaceutical to define an enlarged spleen, as well as the pathological process responsible for its enlargement.


Further study of splenic RES function in a rat leukemia using 99m-technetium-sulfur colloid as a test clearance agent.


Electromyography of the masseter and anterior temporalis muscles in the open-close-clench cycle in temporomandibular joint dysfunction.


The treatment of the temporomandibular joint syndrome.


An analysis of controlled mandibular movement. Kinematographic traces enable an assessment of jaw movements in the sagittal and coronal planes and the relationship of centric relation to centric occlusion can be determined. Centric relation in this context does not necessarily imply the ligamentous position but rather to an actively obtained physiological border position possibly corresponding to the retruded direct contact position. This position in normal subjects is either postero-inferior to or coincident with centric occlusion. Normal subjects were able to make lateral movements of the jaws to and from centric occlusion on either side and certain subjects were able to describe a plateau in or about the horizontal position of centric occlusion. Rhythmic traces showed that opening and closing movements of the jaws could be made in about 550 msec and reflex jaw opening was usually elicited after centric occlusion had been achieved. The significant correlation coefficients found by measuring the angles of opening, terminal opening and closing indicated that jaw movement was integrated. The TMJ series differed from the normal series in nearly all phases of jaw movement recorded. Centric relation was found to be lateral and antero-inferior to centric occlusion. On the side of the first interceptive tooth contact the patient was not able to return the jaws to centric occlusion. Intermittent traces indicated that there was no significant correlation between the angles of opening, terminal opening and closing suggesting that jaw movement were incoordinated. This was reflected in rhythmic traces which were considerably longer than those of the normal series. This increase in duration was found to be due partially to centric slides and partially to asynergistic movements of the mandible. The jaw-opening reflex was not usually elicitable. It is considered that in the TMJ series centric occlusion is a strained position and is usually lateral to and postero-superior to centric relation. This relationship of centric occlusion to centric relation is the reverse of normal relations and indicates that the mandible is displaced in centric occlusion. In general, patients with the TMJ syndrome have a postero-lateral displacement of the mandible.


Letter: Translocation of the Philadelphia chromosome onto the 17 short arm in chronic myeloid leukemia: a second example.


Medical ethics: some uses, abuses, and limitations. A backlash against medical ethics may be developing because of a misunderstanding of its purpose and limitation.  A primary role of medical ethics is to "structure" the disputed issues--i.e., by detailing the relevant principles and implications, analyzing the pivotal concepts, and focusing on the relevant facts.  Medical ethics is limited by being unable to discriminate finely, so that a single line of action can seldom be determined by moral criteria alone.  Underlying many criticisms of medical ethics is the failure to realize that medical ethics as such is not a reform movement or an effort to inspire moral behavior, that it is not and cannot be a specialist's body of esoteric knowledge, that it requires facts and conceptual analyses from other fields to do its work, and that value arguments can be carried farther than one generally expects.


Electromyographic analysis of the effects of treatment in patients with the temporomandibular joint syndrome.


Cell kinetics and practical consequences for therapy of acute leukemia.


Transformation of human cells in culture by N-methyl-N'-nitro-N-nitrosoguanidine.


Radiology of hepatic abscess.

Radiology of hepatic abscess.


Basal-cell carcinoma in office practice.


Medical consequences of teenage sexuality. The occurrence of early marriage, venereal disease, and pregnancy am ong teen-agers in 1973 in New York State (exclusive of New York City) is reported.  During the period, 4740 females and 754 males under the age of 18 were married.  2329 cases of gonorrhea and 32 cases of primary and secondary infectious syphillis were reported.  These figures represent over 11% of the total reported cases of gonorrhea and 7% of the total cases of syphillis in the state for the year.  As a result, a statewide gonorrhea-screening program for females was initiated which revealed that teenagers represented 22.4% of the positive cultures found.  There were 11,078 out-of-wedlock pregnancies, 4989 of which were terminated by abortion.  It is recommended that unrestricted contraception services should be made available to teen-agers as quickly as possible.


Neuroblastoma in adolescence and adulthood.


Presenile dementia.

Presenile dementia.


Medical problems of ear piercing.

Medical problems of ear piercing.


Electrocardiograms of the month.

Electrocardiograms of the month.


Candicidin tablets and ointment in treatment of candidal vaginitis.


Clinicopathologic conference: Severe polydipsia and polyuria.


Case reports: The Swiss connection.

Case reports: The Swiss connection.


Recovery following massive self-poisoning with aspirin.


Circumcision and penile carcinoma.

Circumcision and penile carcinoma.


Systemic lupus erythematosus. Bilateral aseptic necrosis of hip.


Amniotic fluid embolism. Respiratory problem.


Scalene fat pad biopsy. Special indication.


Intermittent diastolic murmur. Caused by coronary artery stenosis.


Thymoma associated with metastatic skin cancer and systemic lupus erythematosus.


Carcinoma of thyroid with metastases to lungs.


Infectious mononucleosis. Retinopathy, fixed pupils, and seizure complications.


Amebiasis. Unusual location in lung.

Amebiasis. Unusual location in lung.


Large-tube drainage of malignant pleural effusion.


Spinal tuberculosis. Treatment by debridement and anterior spine fusion.


Malpractice crisis.

Malpractice crisis.


Geriatrics. Aging and experience forms.

Geriatrics. Aging and experience forms.


Dowstream bacterial emboli.

Dowstream bacterial emboli.


The place of a general intensive care unit in a metropolitan hospital. The results of a six-year survey are given of the admissions, treatment and prognosis of 3310 patients in the intensive care unit at Middlemore Hospital from 1966-72. The range and extent of the treatment underlines both the need for and the value of a general intensive care unit in the integrated daily routine of a large general hospital.


Anaemia in the elderly: caveat caecum.

Anaemia in the elderly: caveat caecum. The experience of a professorial unit over a four-year period of carcinoma of the colon and rectum is described. The high incidence of anaemia in lesions proximal to the splenic flexure is shown. The distressing misdiagnosis of the cause of this anaemia is pointed out, and the consequent misuse of haematinics in the form of blood transfusion, iron and vitamin B12 is shown.


Environmental lead exposure in Christchurch children: soil lead a potential hazard. A study of childhood blood lead levels and of soil lead levels has been carried out in Christchurch. The results indicate a potent hazard especially to the child with unusual appetite for soil. Screening and preventative programmes are briefly discussed.


Carcino-embryonic antigen.

Carcino-embryonic antigen.


Editorial: Practice opportunities.

Editorial: Practice opportunities.


Dural invasion by pituitary tumours.

Dural invasion by pituitary tumours. In 12 cases of pituitary tumour the dura mater of the sella turcica or diaphragma sellae in contact with the tumour was examined histologically. In nine cases tumour cells were found lying deep in the substance of the dura. Dura from the sella of seven subjects without pituitary disease, obtianed at autopsy, showed no inclusions of pituitary tissue. Four of the cases studied were known before death to suffer from an invasive pituitary adenoma. Of eight surviving cases operated upon in the last two years, five showed dural invasion by tumour. The present report suggests that the condition may be more frequent than expected and that with more study it may provide an index of prognosis. It also defines a requirement for the surgeon aiming to prevent recurrence of tumour after operation or to achieve a complete endocrine ablation.


Stevens-Johnson syndrome with hepatitis following therapy with ampicillin and cephalexin. The Stevens-Johnson syndrome is rarely associated with hepatitis and neither entity is commonly seen following the use of ampicillin or cephalexin. An infant is described in whom both entities appeared simultaneously following therapy with these drugs.


Congenital dislocation of the hip in Southland. A study of incidence of congenital dislocation of the hip in Southland was undertaken. Covering as it does a 20-year period during which the common age of diagnosis was reduced from 20 months to three months, this series shows a rising recorded incidence of CDH in a period associated with the arrival of a resident orthopaedic surgeon and introduction of the test of limited abduction with x-ray confirmation. The incidence in the succeeding 10 years rising to 2.9 per thousand live births was between the old average for late diagnosis and that obtained with neonatal examination. A higher incidence among winter births, being twice that of summer, agrees with previously published series. An area of higher incidence on the South coast appears to be explained by two families which include seven of the 25 children born in that zone and 12 of the total 103 in the series. In these two families, the affected children are related by being cousins or second cousins.


The transient nephrotic syndrome of pregnancy. The transient nephrotic syndrome was observed in 24 pregnancies in 23 patients, over a five-year period, in a base hospital obstetric unit. The clinical and biochemical features of this syndrome were similar to the nephrotic syndrome observed in non-pregnant patients. In only half the episodes was the patient a primigravida. In three multigravida patients, previous pregnancies were normal. In 10 of the 24 pregnancies, a perinatal death occurred. A bad fetal prognosis was associated with an early onset of the nephrotic syndrome. Of 11 pregnancies in nine patients occurring after the pregnancy complicated by the transient nephrotic syndrome, seven were normal. One pregnancy was complicated by heavy proteinuria, one by hypertension and intra-uterine death, one by an hydatidiform mole, and one was terminated.


Cyanosis and unrecognised atrial septal defect in children. Two unusual cases of cyanosis and atrial septal defects are presented. Relative hypoplasia of the right ventricle was an associated feature. In both cases cyanosis was the presenting symptom and the usual clinical signs of atrial septal defect were absent. Chest x-rays and electrocardiograms were normal and the correct diagnosis was not made until after cardiac catherisation.


Late presenting, intrarenal haematoma as a complication of renal biopsy. An intrarenal haematoma, necessitating surgical evacuation, is described as a novel, late presenting, complication of percutaneous renal biopsy in a patient with amyloid disease.


Scombroid-type poisoning induced by the ingestion of smoked kahawai. Three incidents of presumptive scombroid poisoning were reported in the Wellington area in 1973. Two of these cases were attributed to canned mackerel and the third to smoked kahawai. The marked similarity of the symptoms of the kahawai poisoning to those of the other two outbreaks of scombroid fish poisoning and the relief following anti-histamine therapy suggests that the poisoning arose from a similar source. Analysis of the extracts from the smoked kahawai revealed an abnormally high level of histamine and the presence of an unknown toxin. The unknown substance resembled saurine, the toxin that has been incriminated in scromboid poisoning, thus suggesting that scombroid intoxication may not be confined to fish belonging to the sub-order Scombroidei.


Letter: Clonidine (Catapres) overshoot.

Letter: Clonidine (Catapres) overshoot.


Letter: Mass miniature radiography.

Letter: Mass miniature radiography.


Letter: Viral gastroenteritis in children.


Christchurch traffic trauma survey: Part 1, Blood alcohol analysis. Some accurate information concerning the drivers involved in traffic accidents was obtained in a survey at Christchurch Hospital. Investigation of these drivers' occupations revealed that a significant proportion came from the semi-skilled and unskilled occupational groups. Alcohol is confirmed as an important factor in traffic accidents and a number of other characteristics of the drivers are described. The dangers of relying on officially-acquired statistics for research work are revealed.


Non-compliance and errors of drug administration in patients discharged from acute medical wards. Three hundred and fifteen patients discharged from acute general medical wards over an 18-month period were studied prospectively to determine deficiencies in medication ingestion from that expected by the hospital clinicians. Thirteen percent did not receive an entirely correct written prescription at the time of discharge from hospital. In 4.5 percent this was the sole reason for treatment failure. Excluding these patients, 40.5 percent of the remainder admitted to medication variations over a 1-6 week period. Non-compliance proved to be a cause of drug default by patients three times as frequently as simple error. Where all errors were considered the ratio was 2 : 1. Whereas non-compliance (indicating volitional intent) was a more common basis for medication variation in Europeans, simple error was a more common cause in Polynesians. Two out of every five of the latter group took incorrect or incomplete therapy because of misinterpretation of instructions, either provided by hospital clinical staff, or printed upon their medication containers. The reasons for non-compliance and simple error are elucidated and the problem of non-delivery of expected medication is discussed. In devising methods for improving accuracy of drug self-administration after discharge from hospital the entities of simple error and non-compliance warrant individual attention.


Letter: Klebsiella infections.

Letter: Klebsiella infections.


A study of the normal range of blood pressure in the aged New Zealand male. A study of blood pressure in males 60 years of age and over, its relationship to age, ideal body weight and time of day, was performed by taking a total of 442 recordings on 133 subjects. No relationship between arterial pressure and increasing age was demonstrable. The relationship between arterial pressure and ideal body weight which exists in other sectors of the population also exists in this age group. In this age group, arterial pressure was not found to vary significantly during the day.


Hyperkinesis and chronic constipation.

Hyperkinesis and chronic constipation. A series of hyperkinetic children (Minimal Brain Dysfunction) is presented, who in part or whole responded to therapy for chronic constipation.


Morals and ethics in medical research.

Morals and ethics in medical research.


Control of venereal disease in New Zealand.


Biochemical studies on the "sucrase" activity in supernatants of human dental plaque material.


Letter: Polyvinyl chloride containers.

Letter: Polyvinyl chloride containers.


Streptococcus salivarius, Streptococcus sanguis and Streptococcus "mitis" as indicators of contamination of root canal cultures. Small samples were taken from the first drop of saliva entering an operation field for root canal treatment isolated by rubber dam, which was intentionally leaky. The samples were primarly cultured in TAS- and BLH-medium and on MS-agar aerobically. The culture media were inoculated directly and via transport medium (VMG III). The cultures were analysed for Strep. salivarius, Strep. sanguis and/or Strep. "mitis" after subculture on MS-agar as soon as visible growth had appeared in the broth media and again after a further 2 days. The following observations were made: 1. Strep. salivarius was almost regularly found in either or both of TAS- and BLH-medium at primary culture of the samples contaminated with saliva. The result was the same whether these broth media were inoculated directly or via VMG III. 2. Strep. salivarius was always found in mixed cultures and was nearly always accompanied by Strep. sanguis and/or Strep. "mitis". 3. Strep. salivarius as well as Strep. sanguis survived two days after visible growth significantly more oftern in BLH-medium than in TAS-medium. The findings lend support to the hypothesis based on clinical studies that when present in root canal cultures Strep. salivarius is ascribable to contamination with saliva.


Denture stomatitis. A histological and microradiographic study of the alveolar mucosa. The alveolar mucosa in the upper jaw from 12 patients suffering from severe denture stomatitis was examined histologically and microradiographically using ultrasoft X-rays. Pathological changes of the epithelial cell layers were observed in all cases. In 10 of the 12 cases examined no keratinization was found. A reduction in the number of epithelial cell layers was commonly observed. In most cases the connective tissue showed signs of moderate to severe inflammation. The inflammatory reaction and the degenerative changes of the tissue were presumably due to a combined effect of microorganisms and mechanical trauma.


Migrating nonerupted lower bicuspids.

Migrating nonerupted lower bicuspids.


Variation of caries frequency with socio-economic background in unselected and extreme groups of 14-year old children in Malmö. The purpose of the present investigation was to find out whether any correlation exists between socio-economic factors and caries frequency in unselected and extreme groups of 14-year old school children in Malmö. The material consisted of 360 randomly selected 14-year old school children in Malmö (1969) and their parents. The number of DF-surfaces was obtained from the records of the school dental service. Data on the parents' occupation and gross incomes in 1969 were obtained from the tax office in Amlmö. Extreme groups were obtained by chosen those 10% with the highest caries frequency (H'-group) and a corresponding group with the lowest frequency of caries (L'-group). These two subgroups were compared with a selection of 14-year old school children with high (H-group) and low (L-group) caries frequency, which have been analysed earlier in respect of socio-economic background. No significant correlation was found between socio-economic factors and caries frequency in the non-stratified selection. H'-group and L'-group, on the other hand, showed marked differences in socio-economic background. Compared with the H-group, the H'-group showed a higher number of DF-surfaces. This difference was due to variations in distribution of caries between different schools but was not clearly correlated to socio-economic factors. The differences in socio-economic distribution between H'-group and H-group like between L'-group and L-group were not found to be significant. The findings mean that the conclusions drawn regarding socio-economic factors and dental care regarding H- and L-group also can be regarded as representative of schoolchildren with extremely high and low caries frequency, respectively.


Radiologic examination: intra oral techniques bisecting angle technique.


Tomorrow--today.

Tomorrow--today.


Prepaid dental plans.

Prepaid dental plans.


Extra-oral technique.

Extra-oral technique.


100 practice locations designated as underserviced for dentistry in Ontario.


Radiologic anatomy in the tooth bearing and contiguous areas.


What's happening in Michigan?

What's happening in Michigan?


What's happening in Pennsylvania?

What's happening in Pennsylvania?


Dentistry and the community college.

Dentistry and the community college.


Pathologic findings in radiographs taken as part of an epidemiological survey in the Sioux lookout zone.


The design of the dental surgery and its equipment.


Delivering dental care in the Canadian North.


A semi-quantitative test for mercury in air.


Observation of the articular disc.

Observation of the articular disc. This article reports on a 5-year study of 198 articular discs of the human temporomandibular joint. The investigation revealed a striking incidence of disc degeneration, notably bilaterally presented. The classification used to qualify the condition of the discs consisted of maximal and minimal degeneration and normalcy. We sought to establish the "norm" for the disc in each successive decade. The fourth decade revealed no degeneration. Disc alteration follows soon after, as shown by the rather high total curve in the fifth decade. Changes are most marked in the fifth, sixth, and seventh decades. There is inconclusive evidence as to the influence of the dentition on disc alteration. However, the view that a complete and/or partial dentition is least likely to contribute to disc problems seems plausible. In general, no one causal agent could be incriminated with certainty.


Oculodento-osseous dysplasia syndrome.

Oculodento-osseous dysplasia syndrome.


Focal epithelial hyperplasia. Report of five new cases from Argentina. Five cases of focal epithelial hyperplasia in Argentina from 1968 to 1974 are reported. There was an age range from 11 to 27 years, with an average of 18 years. Three of the patients were born in Jujuy in the northwest corner of the country. Two of these cases were observed in an epidemiologic study carried out among 8,895 20-year-old Argentine men from different areas.


The staphylococcal scalded-skin syndrome versus erythema multiforme. This article reports a case of scalded-skin syndrome in a young child. Characterized by a generalized exfoliative dermatitis resembling scalded skin, the disease may involve the oral mucosa and must be differentiated from Stevens-Johnson syndrome (erythema multiforme). Since the etiology is specific, the disease can be treated with antibiotics with dramatic results.


Solitary intraductal papilloma of the minor salivary glands. A case of solitary intraductal papilloma of a minor salivary gland is presented. The lesion was diagnosed clinically as a mucocele and has not recurred in 6 months of observation. This case is compared, on the basis of clinical data and histomorphologic findings, to three other known cases. Discussion is made of the role this lesion might play in the etiology of ductal obstruction, and the histologic findings of the intraductal papilloma of minor salivary glands and the solitary intraductal papilloma of the breast are compared.


Benign cementoblastoma (true cementoma). Benign cementoblastoma is a rare benign odontogenic tumor of mesenchymal origin. As only a few documented cases have been reported in the literature, the clinical and histologic criteria for identifying this type of tumor are still uncertain. Thus, problems of differential diagnosis warrant the present report of a case of benign cementoblastoma in the mandible of a 27-year-old man.


Microradiographic description of a crown dilaceration. A case of a crown dilaceration in an upper permanent incisor of a 6-year-old child is described. Microradiographs of sagittal sections demonstrated that enamel was broken into fragments which differed on the vestibular and palatal sides. A study of the structural lines in the dentin layer and the disposition of the enamel fragments permits consideration of the lesion as a consolidated fracture.


The importance of biopsy in endodontics.


Odontomatosis.

Odontomatosis.


Bilateral parotid duct sialoliths.

Bilateral parotid duct sialoliths.


Rhinocerebral mucormycosis: diagnosis and treatment. Report of two cases. Rhinocerebral mucormycosis (phycomycetes), a human fungal disease with oral and perioral findings, has an extremely high morbidity and mortality. The disease is most frequently seen in patients with poorly controlled diabetes. The symptoms, findings, and treatment of rhinocerebral mucormycosis are discussed, and two case histories are presented.


Lip reconstruction following resection for an unusual basal-cell carcinoma. Basal-cell carcinoma most commonly occurs in men in the fifth to seventh decades of life. The area of the lesion is usually one that has frequent exposure to the sun: the middle third of the face and upper lip. An unusual case of basal-cell carcinoma occurring on the lower lip and involving the commissure in a 21-year-old woman is presented. The surgical procedures for resection of the tumor and reconstruction of the commissure are described.


Fractured condyle in a  3-month-old infant. A 3-month-old infant sustained trauma to the mandibular symphysis resulting in radiographic evidence of a fracture of the right condylar head. This presented the diffculty of performing a clinical examination and total reliance on history of a trauma and subsequent swelling. Multiple radiographs of the condyles were used to establish the diagnosis and rule out a film artifact. No definitive treatment was required other than muscle exercises and parental instruction as to potential problems.


Recurring supernumerary teeth. Report of a case.


Coated versus non-Proplast-coated endosseous blade-vent dental implants. In order to determine the efficacy of applying Proplast to dental endosseous bladevent implants, this material was coated on half of sixteen such implants which were bilaterally placed in the mandibles of eight rhesus monkeys. No difference in the clinical acceptability could be ascertained between the two groups. Histologic examination revealed a loose connective tissue layer around the noncoated implants which was not evident around the coated ones.


A sublingual-submandibular calcific mass associated with tumoral calcinosis in a patient with suspected milk-alkali syndrome. The milk-alkali syndrome is a disorder with diverse clinical and biochemical manifestations. It includes three known clinical syndromes. A case of milk-alkali syndrome with associated tumoral calcinosis is presented. The patient developed an unusual oral mass as part of the disease complex. Treatment consisted of excision of the intraoral mass, diet management, and surgical correction of the associated ulcer disease.


Double palate.

Double palate.


Temporomandibular degenerative joint disease. Part I. Anatomy, pathophysiology, and clinical description. The anatomy and function of the temporomandibular joint (TMJ) are described in the detail needed to evaluate and treat temporomandibular degenerative joint disease (TDJD). Innervation of the joint and the mechanism of arthralgia are described and related to TDJD. The clinical course of TDJD, radiographic evaluation of it, histopathologic description, and etiology are presented.


An unusual case of temporomandibular joint ankylosis. An unusual cause of ankylosis of the temporomandibular joint is presented. The treatment plan took into account the potential hazards of major vessel hemorrhage and airway obstruction.


Calcifying odontogenic cyst. A review and analysis of seventy cases. Six new cases of the calcifying odontogenic cyst are presented. These and sixty-four previously reported cases have been studied to further delineate characteristic clinical, radiographic, and histopathologic features of the calcifying odontogenic cyst. A review of the literature with emphasis on the possible histogenesis of the calcifying odontogenic cyst and the nature of the "ghost cells" and their products is also presented.


Maxillary exostoses. Surgical management of an unusual case. A case of an unusually large palatal torus and maxillary exostoses is presented. The preoperative evaluation, including laminagrams, is demonstrated. The surgical approach, with an apparent satisfactory result, is also described.


The elfin facies syndrome.

The elfin facies syndrome. The elfin facies syndrome is characterized by idiopathic infantile hypercalcemia; mental retardation; cardiovascular anomalies, usually supravalvular aortic stenosis and peripheral pulmonary artery stenosis; a peculiar elfin facies and oral anomalies, primarily enamel hypoplasia and oligodontia. The dental features found in the three cases reported include enamel hypoplasia, severe dental decay, oligodontia, pulp stones, microdontia, and abnormally small roots. Some consistent cephalometric abnormalities were thought to contribute to the unusual facial appearance of these patients.


Bacterial endocarditis: a retrospective study. A retrospective study was done on patients admitted to the University of Michigan Hospital from 1962 to 1972 with a diagnosis of bacterial endocarditis. The findings in the group studied indicate that Streptococcus viridans was the predominant causative organism, males were affected three times as often as females, erythromycin was effective against organisms of oral origin, dental procedures were not definitely established as responsible for the onset of the disease in any of the cases, and rheumatic heart disease and congenital heart disease were the predominant, but not the only, predisposing factors.


Juvenile pemphigus vulgaris. Report of a case. Although pemphigus vulgaris rarely occurs in childhood, we herewith report the history of a 19-year-old patient with an apparent 4-year course of pemphigus. In this patient, as in every previously reported case of childhood pemphigus, oral lesions preceded the appearance of skin manifestations. The importance of early biopsy and adequate treatment with adrenocorticosteroids is emphasized.


Verruciform xanthoma. Further light and electron microscopic studies, with the addition of a third case. The authors report their third case of verruciform xanthoma confirmed by electron microscopy and frozen-section lipid stains. Studies of the blood in this case revealed normal levels of triglycerides, cholesterol, and glucose, just as in the previous two cases reported. An ultrastructural search for etiologic factors with the use of material from all three cases resulted in the hypothesis that this lesion is initiated within the epithelium. The authors propose that epithelial entrapment with degeneration and accumulation of lipid may be the logical sequence of early events leading to the formation of foam cells.


X-ray production variability.

X-ray production variability. Some dental x-ray generators do not produce the quantity of x-rays expected at the kilovoltage and milliamperage setting made. A simple experiment was performed on five dental x-ray generators of three manufacturers to test their output in roentgens per minute at a range of kilovoltage and milliamperage settings. Each generator had variable kilovoltage and milliamperage capability. The recorded output was compared with its theoretic output. The results confirm the suspicion that considerable output variations exist and suggest a serious problem to the practitioner wishing to expand his radiographic technique armementarium.


Enamel defects associated with tuberous sclerosis. A clinical and scanning-electron-microscope study. The clinical and scanning-electron-microscope appearances of enamel defects in six patients with tuberous sclerosis are described. The pit-shaped enamel defects seem to be pathognomonic of the disease. The detection may be an important help in the early diagnosis of this complex syndrome.


Relations between tooth positions and focal troughs of panoramic machines. A comparison of the established focal troughs of three panoramic machines with positions of the teeth in the dental arches of 240 patients. The patients, divided into twelve cells, were selected on the basis of race, sex, age, number of teeth, and occlusion. Occlusal registrations were made in fast-set acrylic. Tooth centers were identified and, with the midline-incisal point as a reference point, various composite drawings of tooth positions of patients were made. The total composite of all teeth revealed the striking similarity of the arches. Superimposition on the focal troughs showed that the focal trough of the Panorex easily encompassed all tooth positions. The focal trough of the Orthopantomograph encompassed all tooth positions, although tooth centers lie on the edges of the trough. The focal trough of the GE-3000 with profile index 10 extended so far buccally that many teeth are positioned lingual to the trough. The focal trough of the GE-3000, when reduced uniformly to profile index 7.5, encompasses all tooth positions although some positions fall quite near the borders of the trough.


Double impacted teeth.

Double impacted teeth.


Bilateral idiopathic hypertrophy of the temporomandibular joint articular eminence.


Certain aspects of calcium metabolism studied with morphological and biochemical techniques.


Nucleotide composition analysis of tRNA from leukemia patient cell samples and human cell lines. A technique developed for analysis of less than microgram quantities of tRNA has been applied to the study of human leukemia. Leucocytes from peripheal blood and bone marrow samples of six, untreated leukemia patients and cells of five different established human cell lines were maintained for 18 hours in media containing (32P)-phosphate. Incorporation of radioactive phosphate into the cells from the patient samples was slightly less than that of the cell lines. Likewise, incorporation of (32P)-phosphate into the tRNA of the patient samples (approximately 5 x 106 DPM/mug tRNA) was also less then that incorporated into the tRNA of the cell lines. The major and minor nucleotide compositions of the unfractionated tRNA preparations from each patient sample and each cell line were determined and compared. Similarities and differences in the major and minor nucleotide compositions of the tRNA preparations are discussed with reference to types of leukemia and the importance of patient sample analysis versus analysis of cultured human cells.


Stereochemistry of decarboxylation of trans-4-hydroxycinnamic acid by Aerobacter. The stereochemistry of the decarboxylation of trans-p-coumaric acid to 4-hydroxystyrene by Aerobacter aerogenes has been examined. The decarboxylation has been found to proceed with retention of the geometry about the trans-substituted double-bond.


Remark on the phase problem in crystallography. The ambiguities found in determining a crystal structure from x-ray diffraction can be resolved if one takes into account the random thermal motion of the atoms.


South American mammal zoogeography: evidence from convergent evolution in desert rodents. Current theories regarding colonization of South America by mammals are divided between those supported by fossil evidence, which suggest the original mammal fauna of the isolated continent was augmented by early immigrants (primates, caviomorph rodents, and later, procyonids) with a final large influx of northern mammals occurring with the formation of the Panama land bridge, and an opposing view which states that the purported "recent invaders" are too taxonomically and ecologically differentiated to have colonized since the land bridge arose. The second theory suggests that most extant mammals entered before the Plio-Pleistocene land connection. An analysis of degree of physiological adaptation, natural history, distribution patterns, and a multivariate assessment of convergent evolution of Monte Desert rodents indicate that South American cricetine rodents are not highly specialized for desert life. Their degree of adaptation could be accounted for, in large part, by adaptations for arid or semiarid Andean habitats. No Monte Desert rodent has developed the specialized desert traits that have evolved in most desert rodent faunas of the world, although extinct marsupials similar to living bipedal desert rodents were present in the Monte as recently as late Pliocene. Evidence suggests that Monte caviomorphs have been associated with the desert for a longer period than cricetines, and that the latter represent a fairly recent invasion of the Monte Desert. The data thus support the first hypothesis of South American mammal colonization.


Amino-acid sequence of bovine carboxypeptidase B. The amino-acid sequence of bovine carboxypeptidase B [peptidyl-L-lysine(-L-arginine)hydrolase, EC 3.4.12.3] has been determined using the heavy and light chains of the enzyme isolated from spontaneously activated pancreatic juice. Comparison of the sequence with that of carboxypeptidase A shows that the two enzymes are homologous (49% identity) and that all but one of the functional residues identified in carboxypeptidase A occur in corresponding loci in carboxypeptidase B (peptidyl-L-amino acid hydrolase, EC 3.4.12.2). The exception is the replacement of Ile-255 at the bottom of the substrate binding pocket of carboxypeptidase A, by aspartic acid in carboxypeptidase B. This single change can account for the difference in specificity of the two enzymes.


Activation of adenylate cyclase by phosphoramidate and phosphonate analogs of GTP: possible role of covalent enzyme-substrate intermediates in the mechanism of hormonal activation. Incubation of rat fat pad membranes with 5-guanylyliminodiphosphonate [Gpp-(NH)p] and 5-guanylylmethylenediphosphonate [Gpp(CH2)p], but not GTP (with or without hormones), at 24 degrees or 30 degrees (but not at 4 degrees) greatly stimulates adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] measured after thoroughly washing the membranes. The rate of activation is relatively slow, even with very high (and saturating) concentrations of the analogs. Binding alone appears to be insufficient for activation. Hormones (catecholamines, glucagon) increase the rate but not the extent of activation, even when saturating analog concentrations are used. The dependence on analog concentration (apparent Km) varies with the time of incubation. GTP and very high concentrations of ATP inhibit the activation by Gpp(NH)p, but this effect is dependent on the length of incubation and can be overcome with time. The activated state is not reversed upon incubation of the washed membranes at 30 degrees, even in the presence of GTP, or by solubilization with nonionic detergents. Also, Gpp(NH)p can directly stimulate the control, solubilized enzyme. The activated state of the solubilized enzyme persists upon specific adsorption to and subsequent elution from an organomercurial-agarose column. It is suggested that after forming reversible Michaelis complexes of relatively low affinity, these analogs may react irreversibly with the GTP regulatory site of the enzyme, perhaps forming p(NH)p- and p(CH2)p-covalent enzyme intermediates which capture the activated state of the enzyme. GTP, after binding, may normally activate the enzyme by forming a "labile" pyrophosphoryl enzyme intermediate, and hormone receptors may function to increase the rate of formation (and thus concentration) of this active state of the enzyme.


Visualization of actin fibers associated with the cell membrane in amoebae of Dictyostelium discoideum. Amoebae of Dictyostelium discoideum were attached to a surface coated with polylysine, and the upper portion of the cells was sheared off with a stream of buffer. Scanning and transmission electron microscopy showed that the cytoplasmic surface of the exposed membrane was covered with fibers consisting of actin-containing filaments. The actin was identified by its solubility properties and its ability to interact with muscle myosin.


Molecular model of postsynaptic potential. A molecular model of the excitatory postsynaptic membrane is given in terms of two biochemical cycles intimately associated: an acetylcholine cycle and a calcium cycle. The acetylcholine controls the Na ionophores while calcium ions control the tk ionophore. The two ionophores are spatially separated but interact in such a way that the variation in K conductance precedes that in Na conductance. Digital simulation shows that our model accounts quantitatively for both the evolution of excitatory postsynaptic potential and current in a variety of experimental conditions.


Cooperative activation of action potential Na+ ionophore by neurotoxins. Four neurotoxins that activate the action potential Na+ ionophore of electrically excitable neuroblastoma cells interact with two distinct classes of sites, one specific for the alkaloids veratridine, batrachotoxin, and aconitine, and the second specific for scorpion toxin. Positive heterotropic cooperativity is observed between toxins bound at these two classes of sites. Tetrodotoxin is a noncompetitive inhibitor of activation by each of these toxins (KI = 4-8 nM). These results suggest the existence of three functionally separable components of the action potential Na+ ionophore: two regulatroy components, which bind activating neurotoxins and interact allosterically in controlling the activity of a third ion-transport component, which binds tetrodotoxin.


Distribution of end-to-end distances of oligopeptides in solution as estimated by energy transfer. A homologous series of oligopeptides each containing at its ends a donor and an acceptor of electronic excitation energy was synthesized by the solid-phase method. N-5-(2-Hydroxyethyl)-L-glutamine was the repeating unit, and peptides containing 4, 5, 6, 7, 8, and 9 of these amino-acid residues were prepared. The chromophores naphthalene and dansyl, which were used as donor and acceptor, respectively, fulfil the conditions necessary for energy transfer according to the Förster mechanism. A distance corresponding to 50% efficiency of energy transfer, tro = 22 plus or minus 1 A, was calculated. The kinetics of fluorescence decay of an oligomer containing the naphthalene chromophore only could be described precisely by a monoexponential function. In contrast, the kinetics of the decay curves of the fluorescence of the donor of all of the oligomers containing both donor and acceptor, as measured in viscous solution, deviated markedly from monoexponential behavior. The deviation was interpreted in terms of the great number of different conformations that the various molecules of each of the oligomers attain in solution, leading to characteristic end-to-end distribution functions between the donor and acceptor. Numerical adjustment of the parameters of some of the previously proposed expressions to describe the end-to-end distribution enabled the reconstruction of the kinetics of the fluorescence decay of the donor with great precision. The end-to-end distribution functions for the various oligopeptides were thus evaluated.


Use of biochemical lesions for selection of human cells with hybrid cytoplasms. Techniques for preparing large populations of anucleate cytoplasms from cultured eukaryotic cells have only recently been described. The principal value of anucleate cytoplasms derives from studies that can be done after they are fused to whole cells. Since present methods for the isolation of heterokaryons are unsuitable for the selection of hybrids between whole cells and anucleate cytoplasms (heteroplasmons), a selective system has been developed which is based on the capacity of anucleate cytoplasms containing active enzymes to rescue whole cells poisoned with iodoacetate. Ethidium bromide, a partially effective agent, was used in conjunction with iodoacetate to demonstrate the feasibility of selecting heterokaryons by producing complementary biochemical lesions in the parental cell strains. The potential for artifact in these systems is not, however, entirely precluded.


Transfer of the human gene for hypoxanthine-guanine phosphoribosyltransferase via isolated human metaphase chromosomes into mouse L-cells. We have transferred the human gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferease) via isolated metaphase chromosomes from human HeLa S3 cells into murine A9 cells which lack functional murine HPRT activity, using the technique of McBride and Ozer (Proc, Nat. Acad. Sci. USA 70, 1258-1262, 1973). Three transformed clones were isolated which contained human HPRT activity as determined by electrophoretic and immunochemical assays. Twenty human isozymes other than HPRT whose genes have been assigned to 14 human chromosomes were found to be absent in our transformed clones. Moreover, the human isozymes of hlucose-6-phosphate dehydrogenase (EC 1.1.1.49; D-glucose 6-phosphate:NADP 1-oxidoreductase) and phosphoglycerate kinase (EC 2.7.2.3;ATP:3-phospho-D-glycerate 1-phosphotransferase), whose genes have been linked with the HPRT gene to the long are of the human X chromosome, were also absent. On the basis of the known linkage relationships of the three markers, we thereby suggest that the transferred piece of human genetic material is smaller than 20% of the human X chromosome or less than 1% of the human genome. This estimate assumes a normal syntenic relationship for the long arm of the X chromosome in HeLa S3 cells. In agreement with this conclusion, no human chromosomes could be detected in our transformed clones. When grown under nonselective conditions about 3% of the gene transfer cells lost the human HPRT marker per cell generation. Transformants that had lost human HPRT activity were subjected to hypoxanthine-aminopterin-thymidine selection. The frequency of revertants to the HPRT(+) phenotype was less than 1 x 10(-6), and two revertants that were obtained possessed the mouse electrophoretic phenotype. These results argue against a stable integration of the human donor genetic material into the mouse recipient genome.


Scanning transmission ion microscope with a field ion source. Experiments with a low-resolution scanning transmission ion microscope, using hydrogen ions from a field ionization source, indicate that it will be feasible by this approach to aim at high-resolution ion microscopy. Micrographs of unstained biological specimens have been obtained by critical range absorption of a 55 keV hydrogen ion beam at a resolution of 2000 A.


Subversion of immune system by tumor cells and role of prostaglandins. Mice bearing syngeneic tumors, chemical and virus-induced, became immunologically unresponsive to sheep erythrocytes. The increase in the degree of unresponsiveness with tumor growth suggested a causal relationship. Immunosuppression was in fact caused by the tumor cells because the addition of tumor cells to in vitro cultures of spleen cells and sheep erythrocytes resulted in suppression of antibody response. Suppression was dose dependent with a ratio of 1 to 1000 of tumor cells to spleen cells sufficient to produce significant suppression. Prostaglandins were found to have a role in immunosuppression by tumor cells in that PGE2 was itself immunosuppressive and in that indomethacin and aspirin, inhibitors of prostaglandin synthetases, blocked immunosuppression in vitro and retarded tumor growth in vivo. These findings suggest that tumors, although antigenic, may be able to escape immuno-sureillance by their host by means of subverting the immune system. Thus, success of immunotherapy may well depend on our ability to prevent or block the immunosuppressive activity of tumors.


Induction of endogenous and of spleen focus-forming viruses during dimethylsulfoxide-induced differentiation of mouse erythroleukemia cells transformed by spleen focus-forming virus. Spleen focus-forming virus-transformed erythroleukemic cell clones, which have been established by infection of N type mice with NB trophic Friend virus, continue to release biologically active tfriend virus of NB host range. Dimethylsulfoxide induces erythroid differentiation and a 10- to 100-fold increase in the release of biologically active Friend virus. The increase of Friend virus release is a function of the differentiating erythroleukemic cell. The induced Friend viurs is not the NB tropic Friend virus complex, but shows N host range. The induction of the Friend virus complex is due to simultaneous induction of both spleen focus-forming and endogenous viruses.


Play: early and eternal.

Play: early and eternal. A systematic 12-week investigation of development of play behavior was conducted with eight socially reared rhesus monkey infants. A new, basic and primary play form termed self-motion play or peragration was identified and examined. This behavior follows a human model which includes a wide range of pleasurable activities involving motion of the body through space, e.g., rocking, swinging, running, leaping, and water or snow skiing. It can be argued that self-motion play is the initial primate play form and because of its persistence constitutes a reinforcing agent for maintaining many complex patterns and even pastimes. Monkey self-motion play in the present study was divided into five separate patterns in order to compare the relative importance of social and individual peragration play, the role of apparatus and the overall developmental relationships between the different individual and social self-motion play patterns. The data showed that from 90 to 180 days of age self-motion play was independent of other forms of play, that individual self-motion play appeared earlier and with significantly greater increases in frequency than did social self-motion play, and that apparatus was a necessary component for significant increases in social self-motion play. Other findings were that self-motion play existed independent of locomotion and, though initiated by exploration, was separate from it. Therapeutic implications of self-motion play were discussed.


A protein factor essential for microtubule assembly. A heat stable protein essentail for microtubule assembly has been isolated. This protein, which we designate tau (tau), is present in association with tubulin purified from porcine brain by repeated cycles of polymerization. Tau is separated from tubulin by ion exchange chromatography on phosphocellulose. In the absence of tau, tubulin exists entirely as a 6S dimer of two polypeptide chains (alpha and beta tubulin) with a molecular weight of 120,000, which will not assemble into microtubules in vitro. Addition of tau completely restores tubule-forming capacity. Under nonpolymerizing conditions, tau converts 6S dimers to 36S rings-structures which have been implicated as intermediates in tubule formation. Hence, tau appears to act on the 6S tubulin dimer, activating it for polymerization. The unique ability of tau to restore the normal features of in vitro microtubule assembly makes it likely that tau is a major regulator of microtubule formation in cells.


Identification of human RNA transcripts among heterogeneous nuclear RNA from man-mouse somatic cell hybrids. In man-mouse hybrid line from our cell library, the only cytological detectable portion of the human genome is the X chromosome, and the only genetic markers regularly expressed are coded by genes known to be ?X-linked. A component of the heterogeneous nuclear RNA of these cells was found to be complementary to repetitive human DNA sequences by means of RNA-DNA hybridization on nitrocellulose filters. The same procedure also permitted the identification of hybrid cell DNA sequences that are complementary to human heterogeneous nuclear RNA. This experimental approach, coupled with hybridization studies in situ, is expected to yield critical data on the distribution and the specificity of the repetitive DNA sequences present in the human genome and to provide a new tool for cytological mapping of human chromosomes.


Secretion of a nerve growth factor by mouse neuroblastoma cells in culture. Analyses of supernatant solutions from mouse C1300 neuroblastoma cultures by two independent immunoassays reveal that these cells secrete a factor which is immunochemically similar to mouse submaxillary gland nerve growth factor. The neuroblastoma factor is also biologically active in inducing neurite outgrowth from embryonic sensory ganglia-an effect that is completely blocked by specific antibody to nerve growth factor. Neuroblastoma cells are known to be functionally responsive to nerve growth factor, and the observation that they secrete a molecule like it may mean that these cells require or utilize the factor during growth in culture.


A co-evolution theory of the genetic code. The theory is proposed that the structure of the genetic code was determined by the sequence of evolutionary emergence of new amino acids within the primordial biochemical system.


Methylated, blocked 5 termini in HeLa cell mRNA. Poly(A)-containing HeLa cell mRNA prepared from cells labeled with [methyl-(3)H]methionine or [(32)P]phosphate was found to contain a variety of methylated, blocked 5'-terminal structures of two general types: m(7)GpppN(7)-Np and m(7)GpppN(m)-N(m)-Np. In addition, about one-third of the [(3)H]methyl label was present in the N(6)-methyladenosine; this labeled nucleoside was not found in the 3'-terminal one-third of the mRNA chain and thus may also be in the 5' portion of the mRNA.


Modulation of lymphocyte mitogenesis.

Modulation of lymphocyte mitogenesis. Comparisons of the stimulation of normal lymphocytes and lymphoma cells by tetrameric concanavalin a (Con ta) and dimeric succinyl-Con A suggest that both stimulatory and inhibitory signals operate to modulate mitogenesis. Synergistic effects can be obtained for the stimulatory event using lectins, phorbol esters, and calcium ionophores, all of which are independently mitogenic for lymphocytes. The inhibitory effects of high doses of Con A could be mimicked by the simultaneous addition of the phorbol ester and Con A under conditions in which both reagents are optimally mitogenic when used alone. No inhibition of stimulation was found, however, when succinyl-Con A was used with phorbol ester under the same conditions. Moreover, when lymphocytes were cultured with Con A in the presence of succinyl-Con A, the inhibitory effect of the native lectin was seen at lower doses than in the absence of the derivative. These observations suggest that the stimulatory and inhibitory portions of the dose-response curve can be manipulated independently and may be mediated by two distinct signals. It is likely the signal for the inhibition of cell proliferation is regulated by the same cell surface modulating assembly that controls the mobility of cell surface receptors.


Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites. Injection of frogs with beta-adrenergic catecholamines for 1-24 hr produces marked subsensitivity of the erythrocyte membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1.] to in vitro stimulation by isoproterenol. The subsensitization is specific for catecholamine stimulation, since basal and fluoride-stimulated enzyme activity are unaffected. Maximum isoproterenol-stimulated adenylate cyclase activity declines by 75% in the isoproterenol-treated animals (P less than 0.001). The concentration of isoproterenol causing one-half maximal activation of adenylate cyclase, however, is unaltered. (-)[3H]Alprenolol, a potent competitive beta-adrenergic antagonist, was used to study directly the beta-adrenergic receptor binding sites in the erythrocyte membranes from control and subsensitized animals. A highly significant (P less than 0.005) 60% fall in the number of the beta-adrenergic receptor binding sites ("specific"(-)[3H]alprenolol binding sites) in the treated animals was found. The binding affinity of the sites was not markedly altered. These data suggest that beta-adrenergic catecholamines are able to regulate catecholamine sensitivity of tissues in vivo, by regulating the properties of the beta-adrenergic receptor binding sites.


Radioimmunoassay for melatonin.

Radioimmunoassay for melatonin. Rabbits immunized with human albumin conjugates of N-(p-chlorobenzoyl)-2-methyl-5-methoxyindole-3-acetic acid (indomethacin), 5-methoxytryptamine, and 2-methyl-5-methoxyindole-3-acetic acid produced antibodies that bound [3-H] melatonin. The serologic specificities for the binding of melatonin with antibodies from four antisera to these three immunogens were determined. Melatonin was measurable even at the 0.1 picomole level by a radioimmunoassay. Serotonin, N-acetylserotonin, 5-methoxytryptophol, 5-methoxytryptamine and 6-hydroxymelatonin can be ruled out as immunoreactive material with the use of the multiple antisera of different specificities.


Quantitative determination of splenic red blood cell destruction in patients with splenomegaly. In order to evaluate a method permitting quantitation of splenic red blood cell destruction, a model of erythrocyte destruction in enlarged spleens was created: Erythrocytes are destroyed in the splenic erythrocyte pool at a constant rate, producing in labelling studies hyperhaemolysis due to random destruction. A mathematical analysis of the model shows that the splenic destruction rate can be calculated with great accuracy from quantitation of the initial excess radioactivity, measured over the spleen during the first days after infusion of 51-Cr-labelled autologous erythrocytes. 18 patients with splenomegaly (479-4700 g) were investigated. The splenic erythrocyte destruction rate was estimated to be between 0.5-4.4% of the total erythrocyte mass per day, increasing significantly with increasing splenic weight. The results indicate that erythrocyte destruction takes place almost exclusively in the enlarged spleen in cases of predominant splenomegaly without complicating immunohaemolysis.


Haemolytic anaemia with hereditary pyruvate kinase instability developing acute leukaemia. The case of a 27-year-old woman with pancytopenia, revealing acute monocytic leukaemia and haemolytic anaemia, is described in detail. The underlying cause for the red cell destruction was found to be a pyruvate kinase (PK) instability. Further investigation into three generations of her family (n = 12) disclosed a hereditary PK instability. This was proven by performing biochemical studies to elucidate mutants representing a structurally defective enzyme. Since conversions of pancytopenia with acquired red cell enzyme deficiency into leukaemia have been described, our observation emphasizes that hereditary red cell enzymopathy might also be associated with adult acute leukaemia.


Chromosome abnormalities identified by banding technique in a patient with acute myeloid leukaemia complicating Hodgkin's disease. Chromosome analyses using the Giemsa banding technique were performed on bone marrow cells in a patient with the association of Hodgkin's disease and acute myeloid leukaemia. All cells had an abnormal karyotype showing an extra chromosome No. 14, loss of one chromosome No. 17 and gain of one chromosome No. 18. These abnormalities are in many respects similar to the karyotype changes of lymphoid cells in malignant lymphomas, suggesting a pathogenetic relationship between the two disorders.


Hypocalcemia in leukemia.

Hypocalcemia in leukemia. Hypocalcemia is seen in patients with leukemia and is usually due to renal impairment or to low serum albumin concentrations. Four patients are reported who had hypocalcemia but without these usual explanations. One patient had chronic lymphatic leukemia and overwhelming infections which led to death. The other three patients had chronic myelogenous leukemia in an accelerated phase of the disease characterized by increasing blast cells in circulation, massive hepatosplenomegaly, and myelofibrosis. The cause of the hypocclcemia is unknown.


Angiography in the management of musculoskeletal tumors. The contribution to pretreatment evaluation and surgical planning of 200 angiograms of bone and soft tissue lesions, mostly tumors, was evaluated. Their accuracy was studied  by careful post-operative examination of gross surgical specimens and histologic sections. The angiograms were helpful in delineating the anatomic extent of lesions and, therefore, in planning the appropriate resection or amputation. This was particularly true in lesions treatable by radical local resection, such as most malignant tumors of soft tissues, giant cell tumors of bone, parosteal osteosarcomas, chondrosarcomas and occasional small central osteosarcomas. The angiograms were of some help in confirming or detecting residual or recurrent tumor and prior resection. This was not true immediately after inadequate local resections because residual tumor was likely to be quite small and reactive vascularity secondary to operation was confusing. Angiography was not accurate or helpful in distinguishing benign from malignant lesions when the clinical presentation and roentgenographic findings were confusing. The surgeon relied on biopsy rather than angiography. Aso, although we saw lymph node blushes on several angiograms, we could not reliably interpret whether or not this represented tumor metastasis. The vascularity of pathologic fractures was also confusing. Pelvic angiograms were difficult to interpret because of the complex anatomy. We made most of our serious mistakes in delineating tumor extent in pelvic lesions. Angiography is valuable in planning operative treatment of tumors if radical local resection is considered or if physical examination and roentgenographic findings do not indicate the appropriate level of amputation.


In vitro corrosion studies of a dental gold alloy in contact with cohesive gold and amalgam.


Platelets.

Platelets.


Dummy- and finger-sucking habits with special attention to their significance for facial growth and occlusion.


Fibrinolytic activity in the saliva of patients with coagulation disorders.


Social aspects of treatment in childhood leukaemia.


Interdental gingival clefts.

Interdental gingival clefts.


Warning: sugar can be harmful to your teeth (but not in Dallas schools).


Thoughts on geriatric dentistry.

Thoughts on geriatric dentistry.


Mother cell of megakaryocyte.

Mother cell of megakaryocyte. It was attempted to describe the morphology of the most immature cell of megakaryocytic series. The megakaryocytes were observed with the electron microscope in five cases, being traced back to their immature forms. In two cases the most immature cells of megakaryocytic series were considered to be the cells which were probably identified as lymphocytes under the light microscope, but they were not lymphocytes with the electron microscope. In other two cases it was presumed that neutrophilic and megakaryocytic series were derived from morphologically similar immature cells, since the most immature cells of neutrophilic and megakaryocytic series were not distinguished when they were traced back to their immature forms. These findings suggest that mother cells of megakaryocytes in the adult bone marrow may be identified as lymphoid cells with the light microscope.


Mechanism of platelet liberation.

Mechanism of platelet liberation. Megakaryocytes from 5 patients and 1 normal person were observed electronmicroscopically. In some pathologic states platelets seemed to be liberated without demarcation membrane system (DMS) and in a normal individual they seemed to be liberated independently of DMS. These findings suggest that DMS is not concerned with platelet liberation and that platelets are liberated through pseudopodia and bleb formation. In mature megakaryocytes vigorous amoeboid movement seems to exist and both pseudopodia and blebs may represent this movement. Structural similarity between surface connected system (SCS) of platelet and DMS of megakaryocyte suggests that the structure called DMS is transported as SCS into platelet.


Catecholamines and affective brain disorders.


Anaerobic infections.

Anaerobic infections.


Use of intraocular lenses in cataract surgery.


Metastatic tumors to the kidney.

Metastatic tumors to the kidney.


Felty's syndrome.

Felty's syndrome.


Systolic hypertension (a case report).

Systolic hypertension (a case report).


Editorial: Difficult to trace mothers who ingested DES in pregnancy.


River blindness -- onchocerciases -- a multidisciplinary approach for research and control.


The effect of some local anaesthetics upon the electrical and mechanical activity of respiratory muscles in cats during pentobarbital anaesthesia. No thorough investigation has been made of the effect of small intravenous doses of local anaesthetics upon respiration, although those agents are extensively used for clinical purposes. This prompted a study of the effects of rapid intravenous injections of 2 and 4 mg/kg lidocaine, 3 and 7 mg/kg mepivacaine and 0.4 and 0.8 mg/kg bupivacaine upon the electrical and mechanical activity of the respiratory muscles. Studies were also made of the effects of 3 mg/kg lidocaine when gas mixtures of different carbon dioxide and oxygen content were bein g breathed. The experimental animals were 43 cats, anaesthetized with 35 mg/kg pentobarbital intraperitoneally. Recordings were made of the number of impulses and the maximal impulse frquency from the external intercostal muscles, the diaphragm and the phrenic nerve, together with the tidal volume, minute ventilation, breathing frequency, duration of inspiration, and, during occluded breaths, the maximal pressure and the pressure impulses generated by the inspiratory muscles. It was found that all of the agents investigated had a clear effect upon respiration. The most marked changes became apparent during the first few minutes following the injections, and the effects lasted 10-20 minutes, as judged from changes observed in the recorded parameters. No differences could be seen in the effects of lidocaine and mepivacaine upon respiration, except as regards the effect upon inspiratory time. However, both of these agents differed from bupivacaine in the r effects. Lidocaine and mepivacaine depressed the activity of the external intercostal muscles, whereas the changes recorded from the diaphragm were much less marked...


Primary lymphomas of the central nervous system; in vitro culture observations. Out of 960 human brain neoplasms seven primary lymphomas were cultured and grown up to twenty eight days. The monolayers had common cytological characteristics; /i/ immediately after plantation a high density of uniform cells was observed; /ii/ many cells were lost during subsequent medium changes; /iii/ the monolayers contained lymphocyte-like cells in different numbers. According to their individual characteristics the cultures could be classified into three categories: 1./ In the cultures of three tumours lymphocyte-like cells predominated. These tumours had low proliferative capacity in vitro. 2./ Cultures of three other tumours consisting mainly of tissue macrophages had a high proliferative capacity in vitro. 3./ Cultures of a single tumour showed the combined features of the former two categories: both lymphocyte-like cells, and tissue macrophages were present. These cultures showed the highest proliferative activity. On the basis of these findings it is quite possible that beside other methods, tissue culture technique may be useful in the classification of brain lymphomas.


Ultrastructural study of two central nervous system lymphomas. Electron microscopy was performed on two CNS lymphomas, one primary and the second a skull metastasis from a brain primary lymphoma. The former revealed a tumor perivascularly arranged, which was composed of rounded cells having no specialized organellae. Biopsies from the primary and metastasis of the second case revealed a predominance of rounded cells with scanty cytoplasm, another population of cells with phagocytic activity and a third group with elongated ctyoplasmic processes which stain positively for microglia. By electron microscopy some of these processes resembled neurites or oligondendroglia, while others suggested an astrocytic appearance.


A comparison of the fine structure of malignant lymphoma and other neoplasms in the brain. The fine structure of a primary intracranial lymphoma was examined and compared with that of a group of central nervous system tumors comprised of medulloblastoma, oligodendroglioma, ependymoma, ependymoblastoma. The principal difference was the absence of any junctional devices on the principal tumor cells of the lymphoma and their presence in the other tumors. It is suggested that this difference reflects the difference in origin of these tumors.


The ulstratructure of reticulin.

The ulstratructure of reticulin. The electron microscopic examination of various organs and tumours of different species proved that the ultrastructural equivalent of reticulin fibres is not a uniform substance. Reticulin fibres are either basement membranes or an amorphous mass which appears as argyrophil fibres under the light microscope. Microfibrils may in some cases produce an argyrophilic reticulum. The claimed identity of reticulin and collagen can partly be explained by the chemical similarity of collagen and basement membranes. It seems possible, moreover, that the amorphous mass and microfibrils, which may be an ultrastructural substrate of reticulin, are composed of a material essentially similar to that of collagen.


Cytology of the cerebrospinal fluid in patients with Hodgkin's disease or malignant lymphoma. The cerebrospinal fluids (CSF) of 18 patients with Hodgkin's disease and 33 patients with malignant lymphoma were evaluated for the presence of malignant cells. The CSF  cytology was correlated with the neuropathologic findings at surgery or autopsy. In the 51 patients included in the study there were seven false-negative CSF cytodiagnoses. Methods to improve detection in the false-negatives will be discussed. There were two false-positives. Explanations for the two false-positive cytodiagnoses will be presented. It is concluded that cytological examination of the CSF in patients with Hodgkin's disease and malignant lymphoma is a useful and reliable diagnostic tool.


Electron microscopy of lymphocytic leukaemia cells in the cerebrospinal fluid. The ultrastructure of cells in the CSF are reported in 2 cases of lymphocytic leukaemia of the CNS. Unusual nuclear pockets, margination of the nuclear chromatin and fragmentation of the nuclei were frequent in the first case, whereas in the second nuclear pockets were rare and deep indentations of the nuclei frequent.


Family studies in cases with malignant lymphomas. A short review of the genetic aspects of tumors of the reticuloendothelial system is given. Of special interest is the observation of a "familial lymphohistiocytosis of the nervous system" published by PRICE et al. in 1971. Important are also our own observations with different types of malignant lymphoma in the same family. In addition to the possibilities of classical mendelian inheritance and the possibility of multifactorial inheritance preexisting immunological deficiency syndromes and chromosomal aberrations have to be considered as causal factors.


Radiotherapy of malignant lymphomas.

Radiotherapy of malignant lymphomas. Radiotherapy of non-Hodgkin's lymphomas situated in the central nervous system is basically similar to the treatment applied to any other part of the body. There are two requirements: the first is the prophylactic irradiation of the CNS in a systemic disease of the reticuloendothelial system mainly in acute lymphatic leukemia; the second is the treatment of solitary tumors in the CNS. Radiotherapy can improve dramatically the results obtained with intrathecal chemotherapy, particularly in leukemic involvement of the CNS in childhood. The fractionated single radiation dose should be increased slowly and total doses of 2 500 rd should not be exceeded. Prophylactic radiotherapy of the CNS in acute leukemia has to include the entire subarachnoid space. It is therefore necessary to irradiate the entire skull and spinal cord. This treatment schedule and its results will be discussed. There is a tendency to sue prophylactic radiotherapy in other systemic diseases of the RES as well. The indications and contraindications for this will be discussed. The methods and results of treatment of focal lesions with regard to the morphologic tumor pattern are discussed. Rare primary tumors of the CNS which have the histological features of lymphoma-sarcoma or reticulosarcoma have the best prognosis as far as radiotherapy is concerned.


Lymphoblastic extramedullary spinal tumor during remission of acute lymphoblastic leukaemie. An unusual case history of a girl with ALL is presented. The diagnosis was established at the age of 7. At the age of 11, 5 years and 3 months after remission due to treatment an extramedullary tumour of a lumbar vertebra produced a transverse lesion of the spinal cord and meningeal leukaemia. The tumour consisted mainly of connective tissue with small foci of lymphoblastic cells, identical with those originally seen in the peripheral blood stream. After laminectomy, irradiation and chemotherapy the girl is still in her first haematological remission, lasting nearly 7 years.


Chemotherapy of malignant lymphomas.

Chemotherapy of malignant lymphomas. In malignant lymphomas generally, radiotherapy is the treatment of choice. Chemotherapy cannot be very effective in lymphomas of the CNS because most of the cytostatic drugs in question are not able to pass the blood-brain barrier. But in cases in which malignant lymphomas are disseminated throughout the body including the CNS, cytostatic chemotherapy is the only means of prolonging the life of the patient. In such cases one has to distinguish between Hodgkin's disease and non-Hodgkin lymphomas. Alkylating agents, metaphase inhibitors and antibiotics are used in the treatment of malignant lymphomas. The best results are achieved with combination schedules. In Hodgkin lymphomas the so-called MOPP-schedule is the most effective. In non-Hodgkin lymphomas the same drugs are ususally given without procarbacine. After having achieved a remission, maintenance therapy is very important. Vinblastine and Chlorambuzil are able to prolonge the remission. When resistance to these drugs occurs Bleomycin, Adriamycin, CCNU and Peptichemio are effective agents. The results as well as the side effects of such regimens are described.


Immunotherapy of malignant disease in man. At present active specific immunotherapy should only be attempted where a tumour is shown to be antigenic and immunogenic, patients are immunocompetent, large numbers of tumour cells can be stored and minimal residual disease can be achieved without heavy immunosuppression. Acute myeloblastic leukaema (AML) satisfies such criteria reasonable well and evidence is presented that treatment with BCG and irradiated allogeneic AML cells is of value in this disease. It is suggested that there is insufficient evidence at present to justify embarking on similar regimes in most of the malignant lymphomas.


Meningeal localisation of acute leukaemias. A preventive chemoradiotherapeutic treatment of the central  nervous system has to be started as soon as a complete remission is obtained in acute lymphoid leukemia. Any meningeal localisation is barely sensitive to treatment and reduces the long term chances of survival. The best treatment, according to our study, consists in the intrathecal administration of methotrexate and cytosine arabinoside followed by an irradiation of the central nervous system at a dose of 1,500 rads. The present trials have attempted to reduce the number of intrathecal injections, to increase the irradiation dose to 2,400 rads, and to restrict it to the skull.


Leukoencephalopathy following combined therapy of central nervous system leukemia and lymphoma. We report a from of disseminated necrotizing leukoencephalopathy observed in five children with acute lymphoblastic leukemia or lymphoma, who received systemic chemotherapy, brain radiation, and intrathecal (IT) methotrexate, cytosine arabinoside and hydrocortisone because of meningeal tumor involvement. Three children developed a progressive neurologic disease at the end of IT therapy or shortly thereafter. The lesions consisted in discrete, apparently coalescent foci of coagulative necrosis in the white matter, with a remarkable absence of inflammatory cells, little or no tissue break-down, and striking axonal swellings. The adjacent tissue showed status spongiosus and moderate astrocytic hypertrophy. Vascular lesions were few and inconstant.


The ultrastructure of normal and reactive microglia. Normal microglia have a distinct morphology. In rapidly, but now in slowly evolving pathological states the features used to identify the resting cell are often lost. When there is invasion by haematogenous monocytes, phagocytes develop whose origin - cerebral or haematogenous- cannot be ascertained on morphological features alone. These observations stress that microglia are part of the reticulo-endothelial system.


EM findings on the source of reactive microglia on the mammalian brain. In traumatic brain lesions microglia cells are often plastered on the outer surface of capillaries. Basement membranes delimit these juxtacepillary cells from pericytes and endothelial cells. In altered nervous tissue many stages in the activation of pericytes may be seen at the same time. It is clearly demonstrable that these pericytes attack the basement membrane vigorously from inside. After penetration of the basement membrane these cells propel themselves between the perivascular feet processes of astrocytes and squeeze between the intracellular gaps, becoming surrounded by the cell processes of the neruopil. The observations suggest that in reactive stages in microglia cells may, at least in part, originate from the perivascular mesenchymal tissue.


Experimental studies on kinetics and functions of monuclear phagozytes of the central nervous system. The described experimental studies on rabbits gave evidence of the hematogenous - obviously monocytic - origin, the lymphatic drainage, and the IgG- and complement-receptor sites of monocytoid CSF-cells, epiplexus cells, perivascular cells of the intracerebral vessels, and of some cells within damaged brain tissue - so-called progressive microglia. - Becuase of their identical kinetics and functions these types of mononuclear cells of the CNS were placed in a system known as 'Mononuclear Phagocyte System".


Myxovirus-like particles in cells of American Burkitt's-type lymphoma. Distinct tubular arrays associated with cisternae of endoplasmic reticulum were observed in neoplastic lymphoid cells in a primary American Burkitt's-type lymphoma. A late relapse of the disease was complicated by severe CNS involvement. The pathogenesis of CNS involvement and the significance of the tubular arrays are discussed.


The relationship between microglia and brain macrophages. Experimental investigations. A series of experiments are reported which indicate that the microglia are endogenous cells which may constitute the only source of phagocytes in certain mild degenerative conditions, such as Wallerian degeneration and retrograde nerve cell disintegration. In more extensive lesions with increased vascular permeability a substantial number of the phagocytes are derived from the blood monocytes.


Studies of the mechanism of growth promotion of lymphoma cells by 2-mercaptoethanol in vitro. Rates of incorporation of thymidine and uridine, but not leucine, decrease markedly in L1210 (V) cells within 1 hour of incubation in DULBECCO'S medium containing 10% serum. 2-Mercaptoethanol (2-ME) after a latent period of more than 5 hours causes an increase in nucleotide incorporation. Bovine serum albumin can substitute for serum in the medium, but a higher concentration of 2-ME is required for growth. After charcoal treatment of the albumin less 2-ME is required. These experiments suggest that inhibition of the tumor cells is caused by a serum factor whose effect is antagonized by the thiol.


Acid phosphatase of azurophilic granules of C3HST4 lymphoma. A transplantable mouse lymphoblastic tumor with unusual azurophilic granules has been recently reported. The present tumor has been studied with Gomori and Novikoff methods for lysosomal marker, acid phosphatase. By electron microscopy enzyme was found in granules surrounded by single or double membrane, which displayed a wide morphologic range appearing as 1. vesicular, 2. multivesicular, 3. compound, 4. granular and 5. tubular bodies. The occurrence and the amount of enzyme activity in the granules appeared dependent on their morphology. It was least in vesicular bodies and most in granular organelles, characteristically at their periphery. Since the present tumor, labelled C3HST4, is an unusual rich source of azurophilic granules, it might be useful for further studies of lysosomal bodies. Their functions are poorly understood. Similar structures have been observed in normal human lymphocytes and those from chronic lymphocytic leukemia.


The hypothalamus and vagally mediated gastric relaxation. Experiments, with recording of gastric volume, were performed in chloralosed cats. Topical hypothalamic stimulations produced vagally mediated increases in volume by two mechanisms. One type of response, due to central inhibition of vagal excitatory tone was induced from the defence area and eliminated by atropine or vagotomy. The other type of response, far less commonly encountered, remained after atropine and spinal cord section, but was abolished by vagotomy. The latter type was not induced from any well defined hypothalamic region, and had a high stimulation threshold. While sham feeding in conscious cats with esophagostomy and gastrostomy induced prompt, marked and longlasting gastric volume increases in connection with swallowing, such responses were not evoked as "anticipatory" reaction to food intake;The relaxations could be prevented by vagotomy but not by guanethidine nor atropine. It is concluded that the vagally mediated relaxation in connection with sham feeding occurs mainly from activation of mechanoreceptors and that the hypothalamic control over the vagal relaxatory fibres is probably minor.


Postirradiation syndrome and eeg findings in children with acute lymphoblastic leukaemia. Out of 12 children with acute lymphoblastic leukaemia treated with craniospinal irradiation during primary haematologic remission, 8 developed a postirradiation syndrome characterized by fever and tiredness. The symptoms lasted 1-2 weeks and subsided spontaneously. Longitudinal EEG studies revealed no acute disturbances during the irradiation therapy but in all cases studied, moderate to severe diffuse general slowing developed during the postirradiation syndrome. Complete normalization of the EEG occurred in all children at follow-up. It is concluded that the described EEG abnormalities constitute an integral part of the postirradiation syndrome.


On thorotrast leucaemia. Evolution of clone of bone marrow cells with radiation-induced chromosome aberrations. Results are presented of chromosome studies of bone marrow cells from a 62-year-old woman. The patient had been given 40 ml of Thorotrast in connection with a neuro-radiological examination 34 years earlier. Clinically, the patient was now considered to be in an incipient myeloid leucaemic phase. Ninety-seven per cent of the bone marrow cells belonged to a clone with characteristic marker chromosomes induced by radiation. Few data are available on chromosome analysis of bone marrow cells from Thorotrast patients. Therefore, the results of the present study are compared with data from chromosome analyses of 32P-treated patients with polycythaemia vera, in whom large clones were found in the bone marrow. The results of chromosome analysis of bone marrow cells from the Thorotrast patient support previous hypotheses concerning the carcinogenesis in radiation-induced leucaemia in patients with polycythaemia vera, treated with 32P. In the latter patients, the clone cells are pressumed to represent cell populations with selective qualities, originating from radiation-damaged cells, which possibly possess an increased tendency to malignant transformation because of a more pronounced sensitivity to carcinogenic agents. The cells might also be potentially malignant and manifest themselves as leucaemic cells, if the patient's immunological defence mechanism is broken.


Evaluation of suicide prevention after attempted suicide.


The autoregulation of the microcirculation. The paper reviews August Krogh's contribution to capillary physiology stressing his formulation of useful new concepts such as "tissue cylinder model", capillary intermittency and the intimate matching of capillary perfusion and cellular metabolism. Looked upon from a control theory viewpoint. Krogh was very early in considering the microcirculation as an autoregulated system with tissue oxygen tension as the controlled parameter. Recent work on Krogh's theories is briefly summarized.


Clinical applications of urinary hydroxyproline determination.


Dynamic changes in the microcirculation of diabetics as related to diabetic microangiopathy. Reversible abnormalities of many vascular beds have been observed in early diabetes, before irreversible structural changes of diabetic microangiopathy became apparent. In the bulbar conjenctiva and in the kidney the changes are associated with vascular dysfunction and may be due to autonomic neuropathy. The role of autoregulation in these vascular beds is not clear. In the limb muscles and in the retina the functional abnormality in early diabetes and in those with only mild retinopathy is increased blood flow. This increase in blood flow is probably the result of autoregulatory adaptation to hypoxia induced by 2,3 diphosphoglycerate deficiency. Lactic acid accumulation may also contribute. Breakdown of the autoregulation in the retina results in the development of diabetic retinopathy. The late stages of retinopathy, new vessel formation, are an attempt at revascularisation of areas of capillary non-perfusion.


The ophthalmoscopic and fluorescein angiographic picture of diabetic retinopathy. The ophthalmoscopic and fluorescein angiographic findings in diabetic retinopathy are reviewed. It is pointed out that the fundus lesions seen in diabetic retinopathy are characteristic, but not specific for diabetes. It is still not settled which role alterations in the microcirculation, alterations in the tissue metabolism, hypoxia or defects in the oxygen delivery system may play as provoking factors in the development of the diabetic retinopathy. Future investigations should concentrate on early diabetes and must include studies on the retinal blood-flow, electroretinographic and histopathologic changes.


The problems of tissue oxygenation in diabetes mellitus. III. The "three-in-one concept" for the development of diabetic microangiopathy and a rational approach to its prophylaxis. Evidence for a causative relationship between prolonged tissue hypoxia and diabetic retinopathy and glomerulosclerosis are presented. Based on the assumption that one of the most fundamental requirements for optimal cellular metabolism is a constant cellular oxygen tension, the "three-in-one concept" for the development of diabetic microangiopathy is formulated. The term "three-in-one" is employed because this concept partly or completely includes "the glycoprotein-", "the hypoxia-", and "the growth hormone hypothesis". Diabetics show evidence of variability in the tissue oxygen availability/demand ratio which is compensated by three self-regulating factors: 1) an increase in local flow, 2) an increase in red cell 2,3-DPG leading to a shift to the right of the oxyhaemoglobin dissociation curve, and 3) an increase in the oxygen-binding capacity or the haemoglobin concentration. The level of plasma inorganic phosphate (Pi) is of importance in maintaining high 2,3-DPG levels. However, since Pi fluctuates depending upon changes in the control of diabetes, the regulatory mechanism of the 2,3-DPG modulated unloading of oxygen from the erythrocytes often becomes insufficient, and therefore in poorly regulated diabetics with less than optimal 2,3-DPG levels, the main load of compensation against tissue hypoxia is placed on an adjustment in the microcirculation of the organ involved. However, in order for the microvascular dilatation to occur, the cells must experience a hypoxic stimulus. The summation of the infinite number of discrete and occasionally pronounced hypoxic injuries to the tissue cells in association with the adverse effect of local vasodilatation with increased plasma permeation through the vessel walls might over the years lead to diabetic microangiopathy. Based on this theory the high level of Pi in diabetes becomes of particular significance. Our experience with a high phosphate diabetes diet in the treatment of diabetics is presented. This dietary regimen leads to a significant increase in the oxygen release capacity of the erythrocytes, suggesting an improvement in tissue oxygenation, and may therefore become of value in the prophylaxis of diabetic microangiopathy.


Peripheral retinal microaneurysms in chronic leukemia. Of 25 patients with chronic leukemia, there was clinical evidence of peripheral retinal microaneurysm formation in two of eight patients with chronic lymphocytic leukemia and six of 17 patients with chronic myelogenous leukemia. There was no proliferative retinopathy in any of the 25 patients. An elevated leukocyte count seemed necessary for microaneurysm formation in leukemia, although some patients with elevated counts had no microaneurysms. The prolonged leukocytosis of chronic leukemia can produce peripheral capillary dropout, vascular stagnation, microaneurysm formation, and, rarely, peripheral proliferative retinopathy similar to sickle cell disease.


Lipid composition of the mouse spleen in Rauscher leukaemia. Lipid constituents were examined in the spleen of mice 10, 14 and 18 days after infection with Rauscher leukaemia virus. (i) The total lipid content, as related to the amount of protein, decreased with the development of the tumour. (ii) Spleen cells of control and infected mice synthesized the same lipids. (iii) In the infected spleen, free fatty acids increased by 80% and triglycerides decreased by 44% as compared to the control. The percentage distribution of phospholipid components showed a change in tumour cells: lecithin and phosphatidylethanolamine increased, lysolecithin and sphingomyelin decreased. (iv) After intraperitoneal injection of [32P] orthophosphate, in infected mice the incorporation of 32P into phosphatidylcholine and phosphatidylethanolamine increased, while 32P incorporation into lysophosphatidylcholine + sphingomyelin and phosphatidylinositol + phosphatidylserine fractions decreased.


Basis for late expiratory spinal inhibition of phrenic nerve discharge. The relationship between spinal inhibition of phrenic nerve activity and thoratic expiratory motoneuronal discharge was studied in chloralose-anesthetized and unanesthetized decerebrate cats.  The amplitude of the phrenic nerve response elicited by singleshocks applied to descending tracts in the second cervical spinal segment progressively fell during the late expiratory phase of the central respiratory cycle.  The depression resulted, at least in part, from active spinal inhibition since the spina-to-phrenic evoked response was smaller in late expiration than after C'1 spinal transection.  Inhibition of the spinal-to-phrenic evoked was time-locked to the spontaneousburst of activity recorded from the eigth internal intercostal nerve.  The degree of inhibition of the spinal-to-phenic evoked discharge was directly related to theamplitude of spontaneously occurring internal intercostal nerve activity.  A similiarrelationship was observed when internal intercostal nerve activity and spinal inhibitionof phrenic discharge were evoked by stimulation of the superior laryngeal nerve.  It is concluded htat late expiratory spinal inhibition of phrenic discharge was dependent on those neural events responsible for the activation of thoracic expiratory motoneurons.


Glucocorticoid binding proteins in myeloblasts of acute myelogenous leukemia. The myeloblasts of 16 patients with untreated acute myelogenous leukemia were examined for specific glucocorticoid binding proteins. In only 3 of the 16 patients were such high affinity receptors found. The presence of glucocorticoid binding protein activity was positively correlated with inhibition of macromolecular synthesis of myeloblasts in vitro whereas absence of binding protein activity was associated with lack of glucocorticoid inhibition of the cells. Since glucocorticoids appear efficacious in only a small fraction of cases of acute myelogenous leukemia, determination of glucocorticoid binding protein activity may provide assistance in planning chemotherapeutic regimens.